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7 recordsLinked to original sources
PubMed2026

Non-motor symptoms and healthcare utilization before diagnosis of myasthenia gravis: a nationwide cohort study.

BACKGROUND: Non-motor symptoms have been reported prior to myasthenia gravis (MG) diagnosis. However, the temporal patterns of non-motor symptoms and healthcare utilization before MG diagnosis remain unclear. METHODS: We conducted a retrospective, population-based cohort study using the Korean National Health Insurance Service (KNHIS) database from 2011 to 2021. Incident MG cases were identified using the International Classification of Diseases, Tenth and Rare Intractable Disease codes. Individuals younger than 20  years or with missing health screening data were excluded. Each MG case was matched 1:10 by age, sex, and index date to controls. Non-motor symptoms and healthcare utilization were defined using operational criteria derived from KNHIS claims data. Rate ratios (RRs) and 95 % confidence intervals (CIs) were estimated across four prespecified intervals (0-1, 1-2, 2-5, and 5-10  years) before MG diagnosis. RESULTS: We included 8,355 MG patients and 83,550 controls (mean age, 53.7  years; male, 44 %). MG patients had higher rates of any non-motor symptoms over 10  years(RR 1.34; 95 % CI 1.30-1.39), with the sharpest increase in the year before diagnosis. Depression, anxiety, migraine, constipation, and insomnia consistently showed higher RRs across all intervals. Hospitalizations (RR 1.66; 95 % CI 1.61-1.71) and outpatient clinic visits (RR 1.10; 95 % CI 1.04-1.17) were consistently higher across 10  years, peaking during the 0-1 year before MG diagnosis. CONCLUSION: Non-motor symptoms and healthcare utilization increased years before MG diagnosis. Earlier recognition of these symptom patterns may facilitate timelier evaluation for MG and improve diagnostic pathways.

Humans↗
PubMed2026

ACE2 and Parkinsonism‑related bone metabolic alterations: signaling pathways and hub gene analysis.

Clinical co-occurrence of Parkinson's disease (PD) and age-related bone loss in elderly patients has garnered increasing attention, yet its molecular mechanisms remain incompletely elucidated. This study used an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in Ace2-/y mice to investigate the regulatory mechanisms of bone-brain axis-related genes and signaling pathways. Behavioral tests assessed motor and non-motor symptoms. Immunohistochemistry, Western blot, and histopathological staining analyzed dopaminergic neuron activity, microglial activation, and bone metabolic abnormalities. GEO dataset transcriptomics and weighted gene co-expression network analysis (WGCNA) identified key hub genes, with receiver operating characteristic (ROC) curves evaluating their diagnostic value in public single-disease transcriptome data. MPTP significantly exacerbated motor dysfunction and depression-like behaviors; Ace2 deletion lowered total Wnt, β-catenin, BMP and IGF-1 protein abundance alongside reduced phosphorylation ratios of their downstream kinases in brain and bone, while upregulating RANKL/RANK/OPG-associated inflammatory mediators, accompanied by elevated total α-synuclein, Casp3 and Bax protein levels. The parallel reduction of these signaling proteins only suggests potential perturbation of related cascades; WGCNA identified 10 hub genes (e.g., DNM1, OCRL, OPA1), whose dysregulation was linked to synaptic dysfunction and inflammation. ROC analysis based on single-disease datasets showed high diagnostic accuracy for PD and `osteoporosis (OP) (AUC: 0.683-0.981), with core genes influencing synaptic, MAPK, Rap1, and Ras pathways. These preclinical findings indicate that Ace2 deficiency is associated with concurrent pathological abnormalities in the brain and transient bone metabolic disturbance under short-term MPTP treatment in growing young male mice; coordinated dysregulation of shared signaling pathways was observed in the two tissues, consistent with a potential bone-brain axis pathological phenotype, though causal bidirectional tissue cross-talk cannot be confirmed in the current experimental design, providing candidate targets that warrant further validation.

Animals↗
PubMed2026

Essence: A benchmarking-validated transformer framework for early diagnosis of Parkinson's disease using cerebrospinal fluid protein biomarkers.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. The lack of objective molecular biomarkers limits early diagnosis and personalized treatment. Here, we propose Essence, a benchmarking-validated framework integrating cerebrospinal fluid (CSF) proteomics with traditional and deep learning models to identify robust protein signatures for PD. Using data from two independent cohorts, 1266 high-confidence proteins are quantified, among which 178 exhibit differential abundance between PD and healthy controls (HC). Through systematic benchmarking of ten machine learning algorithms and four neural architectures, the Transformer model consistently outperforms alternatives across multiple feature selection strategies, achieving an area under the receiver operating characteristic curve (AUC) of 1.0000 with only 35 features. Functional analyses of the top-ranked 35 proteins reveal enrichment in neuroinflammatory, synaptic, and oxidative stress-related pathways. Importantly, spatial transcriptomic profiling based on the Allen Brain Atlas shows region-specific expression of these biomarkers in PD-relevant brain structures, including the striatum, subthalamic nucleus, hippocampus, and white matter tracts. This anatomical alignment supports the functional relevance of the identified markers and highlights their potential utility in early-stage diagnosis and mechanistic understanding of PD.

Benchmarking↗
PubMed2026

Intra-locus coeruleus LPS administration induces anxiety-like behavior, thermal hyperalgesia, and striatal lysosomal alterations: Relevance to Parkinson's disease.

According to Braak's staging hypothesis, Parkinson's disease (PD) pathology may originate in extranigral regions, including the locus coeruleus (LC). In parallel, PD has been associated with lysosomal dysfunction. Here, we investigated whether intra-LC lipopolysaccharide (LPS) injection may produce behavioral alterations and lysosomal protein changes in the striatum and prefrontal cortex (PFC), regions critically implicated in PD pathology. Adult male Wistar rats received unilateral injections of saline or LPS (10 µg/2 µL) into the LC or striatum and were assessed for anxiety-like behavior, thermal hyperalgesia, and motor coordination. A separate cohort was sacrificed 15 days post-injection to assess lysosomal proteins (cathepsin D, β-glucocerebrosidase, Lysosomal Associated Membrane Protein 2 (LAMP2)) and α-synuclein (α-Syn). Intra-LC LPS induced anxiety-like behavior, reflected by reduced time spent in the center of the open field, and thermal hyperalgesia, as shown by shortened tail-flick latency, whereas intra-striatal LPS impaired locomotion and motor coordination, evidenced by reduced line crossings and decreased rotarod performance. Intra-LC but not intra-striatal LPS reduced LAMP2 levels in the striatum, while all other markers remained unchanged in both regions. These findings provide experimental support for Braak's hypothesis.

Animals↗
PubMed2026

Efficacy of citicoline as an add-on therapy in Parkinson's disease: a randomized, double-blind trial.

BACKGROUND: Citicoline is a promising therapeutic option for improving both motor and non-motor symptoms in Parkinson's disease (PD) beyond levodopa and other standard dopaminergic treatments. OBJECTIVES: The CITIPARK study evaluated the efficacy and safety of citicoline in improving clinical outcomes and quality of life (QOL) in PD patients on dopaminergic therapies. METHODS: The randomized, double-blind, multicenter trial compared citicoline (1000 mg/day intramuscular, two six-week cycles) with placebo for 24 weeks in PD under stable medications. The primary endpoint was change in Movement Disorder Society-Unified PD Rating Scale (MDS-UPDRS) total score; secondary endpoints included motor and non-motor subscores, QOL, clinical global impression (CGI) and safety. RESULTS: The study enrolled 485 participants, randomizing 474 (citicoline: 303; placebo: 171). Citicoline significantly increased the likelihood of achieving a minimal clinically important difference compared with placebo (OR 2.06, 95% CI 1.06-3.99; P = 0.031) on the MDS-UDPRS total score in the modified intention-to-treat population. Among secondary outcomes, the citicoline group showed greater improvement in motor function (MDS-UPDRS III -2.97 vs -0.13; p = 0.009) and a greater improvement on CGI -II and CGI-III (3.26 vs 3.59; p = 0.021 and 9.30 vs 10.38; p = 0.018, respectively). AEs occurred in 22.1% and 27.1% of the citicoline and placebo groups, respectively. CONCLUSIONS: Citicoline was well tolerated and associated with motor benefits compared with placebo in a highly compliant population. The results suggest a role of citicoline as a safe and possibly effective supportive therapy in PD treated with concomitant dopaminergic agents.

Humans↗
PubMed2026

Comparison of Proteomic Analysis of Cerebrospinal Fluid From Neurological Patients With and Without Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterised by progressive muscle weakness in both bulbar and extremity muscles, leading to a diverse clinical phenotype with motor and non-motor symptoms. Approximately 85% of ALS cases are sporadic (sALS), while the remaining 10%-15% are familial (fALS). Biological biomarkers of sporadic ALS remain poorly understood, hindering precise patient screening, delaying diagnosis and negatively affecting prognosis. This study aims to identify potential proteomic biomarkers by comparing the cerebrospinal fluid (CSF) of sALS patients with that of patients suffering from other neurological diseases. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for proteomic profiling of CSF samples from 24 sALS patients and 26 patients with other neurological diseases. The complete protein expression profiles were compared using a two-tailed Student's t-test, with a p <&#x2009;0.05 considered statistically significant with additional FDR correction at the 0.1 level. Proteomic analysis of CSF samples identified significant quantitative changes in 96 proteins with threshold p&#x2009;<&#x2009;0.05 and 74 proteins with FDR <&#x2009;0.1 between sALS and non-ALS patients, including alterations in proteins associated with neurodegenerative processes, such as amyloid precursor proteins and inflammatory markers. CSF proteomic analysis reveals altered inflammatory and neurodegenerative metabolic pathways, providing valuable insights into the proteomic landscape of sALS. Several dysregulated proteins were consistent with the disease mechanisms highlighted in previous studies. These findings represent a step forward in developing personalised approaches for diagnosing and managing the disease.

Humans↗
PubMed2026

Effects of Fecal Microbiota Transplantation on Intestinal Microbial Characteristics and Clinical Phenotypes in Patients with Parkinson's Disease.

Alterations in the gut microbiota have been associated with Parkinson's disease (PD), but longitudinal microbial changes after fecal microbiota transplantation (FMT) and their clinical associations remain poorly understood. This single-center retrospective observational study included 6 patients with PD, stratified into high- and low-severity subgroups based on disease duration (>6 years vs &#x2264;6 years). Thirty-six fecal samples were collected before FMT and monthly for five months afterward. Microbial diversity, community structure, taxonomic composition, and predicted functional profiles were assessed using 16S ribosomal RNA gene sequencing. Analyses included alpha and beta diversity, taxonomic abundance, linear discriminant analysis effect size, Tax4Fun2-based functional prediction, and Spearman rank correlations between microbial features and clinical indicators. Descriptive analyses indicated differences in microbial richness, diversity, community structure, and predicted functions between severity subgroups and across post-FMT time points. At baseline, the low-severity subgroup had greater microbial richness and diversity than the high-severity subgroup, with relatively higher abundances of taxa including Bifidobacterium and Lactobacillus. One month after FMT, richness and diversity increased from baseline in the high-severity subgroup, accompanied by changes in taxonomic composition. Both subgroups showed time-associated variation in microbial diversity and predicted Kyoto Encyclopedia of Genes and Genomes pathway enrichment after FMT. Predicted functions included carbohydrate and amino acid metabolism, secondary metabolite biosynthesis, membrane transport, and signal transduction. Several operational taxonomic units correlated with indicators of motor impairment, constipation, sleep quality, functional status, and neuropsychiatric symptoms. FMT was therefore associated with longitudinal changes in gut microbial diversity, composition, and predicted functions, and specific microbial features were associated with motor and non-motor indicators. Given the small retrospective cohort, these findings are preliminary and warrant confirmation in larger controlled studies. Future studies should determine whether these microbial alterations are reproducible, persist beyond five months, reflect donor engraftment, and correspond to measurable clinical improvement after transplantation in PD.

Humans↗